In vivo effects of hyperosmotic perilymph perfusion on hair cell and neural potentials

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The effect of osmotic bias on cochlear potentials was investigated by perfusion of scala tympani with a modified artificial perilymph. The mean osmolality of the artificial perilymph was increased by around 15% (from 303 ± 6 mOsm/kg H2O to 349 ± 1 mOsm/kg H2O) by addition of sucrose. OHC function was assessed using Boltzmann analysis of the low-frequency CM. Neural thresholds and waveforms were monitored at multiple frequencies, and spontaneous neural noise was monitored via a round-window electrode. The 2-minute perfusions caused a 6 ± 4% increase in the maximal CM amplitude, indicating an increase in OHC basolateral permeability, and an 8 ± 1% increase in MET sensitivity, which may reflect a decrease in OHC axial stiffness. The operating-point shifts recorded were more variable: in healthy animals, the hyperosmotic perfusions caused initial operating point shifts towards scala vestibuli of around 1 – 2 meV that were either followed by a brief undershoot towards scala tympani, or initiated a longer-lasting scala tympani operating point shift. Nonetheless, these operating point shifts were smaller than expected, resulting in a less than ±2 meV deviation from the starting point. Neural thresholds during the perfusion fell (by 20 – 30 dB at 22 kHz), and recovered with a time course consistent with the predicted perilymphatic sucrose concentrations at the corresponding BM place for each frequency. The mechanism of the changes observed with these hyperosmotic perfusions is not known, but its effects were not consistent with a simple movement of the reticular lamina towards scala vestibuli. Other data (Marcon and Patuzzi, in preparation) indicate the CAP threshold shifts during these perfusions are most likely mechanical in origin. The experimental results from the guinea pig are compared with simulated perfusions carried out in a mathematical model of cochlear regulation based on the ionic transport mechanisms and motile properties of the outer hair cells.